The proposed program seeks to develop and/or perfect methodology for the comprehensive analysis of the biologically active fractions of marijuana smoke condensate (MSC). Marijuana (two types) and tobacco (one type) will be burned using two smoking conditions to produce six condensates. Each condensate will be fractionated via identical processes. The Ames/Salmonella assay will be applied to all crude material and fractions in order to assess their mutagenic properties. Analytical method development will be directed towards those fractions that are bio-active. The program will apply (or develop) methods to analyze the volatile as well as the non-volatile portions of each active fraction. Where necessary, subfractionation using chromatographic techniques will be utilized. For characterization (and comparison) of marijuana and tobacco volatiles, gas chromatography/mass spectrometry will be the principal method. For the non-volatile (heretofore uncharacterized) constituents, liquid chromatography/mass spectrometry is proposed. The development of radially compressed, micro-bore packed liquid chromatography systems is a goal of this project. It is anticipated that, with the methods used/developed under this program, procedures for the characterization of samples that are potentially carcinogenic will be available to NIDA. Such methods will be applicable to virtually any smoke condensate or similar matrix.